(1) The control of the galactose operon in E. coli is studied as a model for gene regulation. We have demonstrated that the regulation of this operon is exerted by two overlapping promoters P1 and P2. The cyclic AMP receptor (CRP) and cyclic AMP (cAMP) activate only P1; gal repressor inhibits transcription from P1 only. P2 is repressed by CRP and cAMP and is probably subject to another regulatory mechanism. We have determined the nucleotide sequence of the entire regulatory region for the wild type gal operon and the base changes in several mutants in this region. This operon constitutes an excellent model system for the study of complex genetic regulation. (2) In collaboration with Dr. Ira Pastan, we are studying the changes in cellular gene expression which occur when animals cells are transformed by oncogenic viruses. We have demonstrated that the levels of translatable mRNA for two large extracellular proteins, the Cell Surface Protein and Collagen, are considerably reduced in transformed cells. These two proteins play an important role in the cellular interactions between normal cells. We are preparing DNA probes which will enable us to directly measure the levels, rate of synthesis and half-life of mRNAs for collagen and other transformation sensitive proteins in different lines of normal and transformed cells and in differentiating tissues. BIBLIOGRAPHIC REFERENCES: Howard, B.H., de Crombrugghe, B., and Rosenberg, M.: Transcription in vitro of Bacteriophage Lambda 4S RNA: Studies on Termination and rho Protein. Nucleic Acids Res. 4: 827-842, 1977. Musso, R., DiLauro, R., Rosenberg, M. and de Crombrugghe, B.: Nucleotide Sequence of the Operator-Promoter Region of the Galactose Operon of Escherichia coli. PNAS 74: 106-110, 1977.